Biomedical subjects

K Nozaki

Publications and source records attributed to K Nozaki.

At least 19 recordsLinked to original sources

PubMed2006

Inheritance pattern of familial moyamoya disease: autosomal dominant mode and genomic imprinting.

BACKGROUND: Although the aetiology of moyamoya disease (MMD) has not been fully clarified, genetic analysis of familial MMD (F-MMD) has considerable potential to disclose it. OBJECTIVE: To determine the inheritance pattern and clinical characteristics of F-MMD to enable precise genetic analyses of the disease. METHODS: 15 highly aggregated Japanese families (52 patients; 38 women and 14 men) with three or more affected members were examined. The difference in categories of age at onset (child onset, adult onset and asymptomatic) between paternal and maternal transmission was compared by chi2 statistics. RESULTS: In all families there had been three or more generations without consanguinity, and all types of transmission, including father-to-son, were observed. Among a total of 135 offspring of affected people, 59 (43.7%) were patients with MMD or obligatory carriers. Affected mothers were more likely to produce late-onset (adult-onset or asymptomatic) female offspring (p = 0.007). CONCLUSIONS: The mode of inheritance of F-MMD is autosomal dominant with incomplete penetrance. Thus, in future genetic studies on F-MMD, parametric linkage analyses using large families with an autosomal dominant mode of inheritance are recommended. Genomic imprinting may be associated with the disease.

Adolescent↗

PubMed2005

Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins.

Bone morphogenetic proteins (BMP) induce bone formation in vivo, and clinical application in repair of bone fractures and defects is expected. However, appropriate systems to deliver BMP for clinical use need to be developed. We synthesized a new synthetic biodegradable polymer, poly-D,L-lactic acid-para-dioxanone-polyethylene glycol block copolymer (PLA-DX-PEG), to serve as a biocompatible, biodegradable polymer for recombinant human (rh) BMP-2 delivery systems. In animal experiments, new bone was efficiently formed and a large bone defect was repaired using PLA-DX-PEG/rhBMP-2 composites. In addition, this new polymer could be used as an injectable delivery system for rhBMP-2. The rhBMP-2/PLA-DX-PEG composites also could be combined with other materials such as hydroxyapatite or titanium. This new synthetic polymer might be used for rhBMP-2 delivery in various clinical situations involving repair of bone, leading to great changes in orthopedic treatment.

Animals↗

PubMed2005

The Healthgrid White Paper.

Over the last four years, a community of researchers working on Grid and High Performance Computing technologies started discussing the barriers and opportunities that grid technologies must face and exploit for the development of health-related applications. This interest lead to the first Healthgrid conference, held in Lyon, France, on January 16th-17th, 2003, with the focus of creating increased awareness about the possibilities and advantages linked to the deployment of grid technologies in health, ultimately targeting the creation of a European/international grid infrastructure for health. The topics of this conference converged with the position of the eHealth division of the European Commission, whose mandate from the Lisbon Meeting was "To develop an intelligent environment that enables ubiquitous management of citizens' health status, and to assist health professionals in coping with some major challenges, risk management and the integration into clinical practice of advances in health knowledge." In this context "Health" involves not only clinical procedures but covers the whole range of information from molecular level (genetic and proteomic information) over cells and tissues, to the individual and finally the population level (social healthcare). Grid technology offers the opportunity to create a common working backbone for all different members of this large "health family" and will hopefully lead to an increased awareness and interoperability among disciplines. The first HealthGrid conference led to the creation of the Healthgrid association, a non-profit research association legally incorporated in France but formed from the broad community of European researchers and institutions sharing expertise in health grids. After the second Healthgrid conference, held in Clermont-Ferrand on January 29th-30th, 2004, the need for a "white paper" on the current status and prospective of health grids was raised. Over fifty experts from different areas of grid technologies, eHealth applications and the medical world were invited to contribute to the preparation of this document.

Computer Communication Networks↗

PubMed2005

The first grid for the oral and maxillofacial region and its application for speech analysis.

OBJECTIVES: Introduction of a new grid-based method for analyzing speech functions which takes into account the related information of patients' data and the oral air flow with pronouncing analyzed by computational fluid dynamics. METHODS: An on-line speech analyzer was developed for clinical use utilizing GridPort2.3.1 based on globus2.4.2, comprising several computational tools such as unified data storage, semantic data analysis, computational fluid dynamics analysis and three-dimensional visualization of calculated results from different hardware sources with various types of operation systems. RESULTS: The power transportation layer between dental clinics and computational and storage resources could be provided by using a WWW-based portal. The backend data management system could be constructed using a storage resource broker (SRB) and extensible mark up language (XML). CONCLUSIONS: The new method allows the construction of a data warehouse through this grid-based speech function analysis in order to extract the principal factors related to speech disorders.

Database Management Systems↗

PubMed2004

Starch properties of the sago palm (Metroxylon sagu Rottb.) in different soils.

We investigated the relationships between starch concentrations and activities of starch synthetic enzymes in sago palms (Metroxylon sagu Rottb.) under acid sulfate and mineral soil conditions. Plants grown naturally that had reached their maturated stage were sampled. We found that the growth in acid sulfate soil is lower than that in mineral soil and that starch granules were larger and there was more amylase activity in acid sulfate soil than in mineral soil. Lower amylase activity in mineral soil could eliminate the degradation of starch, making the smaller granules suitable for storing large amounts of starch in a limited space inside cells.

Amino Acid Sequence↗

PubMed2003

Release of recombinant human bone morphogenetic protein 2 from a newly developed carrier.

After implantation of a polymer-coated gelatin sponge (PGS) containing either 0.4 or 1.0 mg of 125I-rhBMP-2 for each 1 cm(3) of PGS into the right ulnar of rabbits, changes in the level of radioactivity at the implant site and in the blood were measured for 21 days after implantation, and the cumulative excretion ratio of radioactivity in the urine and feces was calculated. For both doses, radioactivity at the implant site was eliminated biphasically. The concentration of trichloroacetic acid (TCA)-precipitable radioactivity in the blood reached a maximum 6 h after implantation, at which time it was equivalent to 1.41% of the administered dose (0.4 mg/cm(3)). The remaining radioactivity was eliminated rapidly thereafter, falling below the detection limit within 48 h. The t(1/2alpha) was about 0.1 days, the t(1/2beta) was about 3 days, and the mean resident time (MRT) value was about 4 days. By 17 days after implantation, 88.1% of the administered radioactivity had been excreted in the urine, and 1.7% had been excreted in the feces. TCA precipitation test results indicated that most of the radioactivity excreted in urine was a low-molecular weight decomposition product. At 21 days after implantation, the radioactivity of the PGS implant site had declined to 0.5% of the administered amount. Autoradiographs of the implant site taken 28 days after implantation revealed that, at both doses, the residual radioactivity was confined to the area of the implanted PGS. These results indicate that PGS retains an appropriate amount of recombinant human bone morphogenetic protein 2 (rhBMP-2) at the orthotopically implanted site for at least 21 days enough to induce bone regeneration. Thus, PGS shows great clinical potential as a carrier for rhBMP-2.

Animals↗

PubMed2003

Local bone formation by injection of recombinant human bone morphogenetic protein-2 contained in polymer carriers.

The regenerating potential of human bone is limited. The repair of large bone defects often associated with bone tumor resections is not observed, and nonunion or delayed union of bone is a serious problem for fracture treatment. In these cases, autogeneic or allogeneic bone grafting has been routinely indicated, but these approaches require invasive surgical procedures. An alternative approach described in this paper involves the injection of bone morphogenetic proteins (BMPs) in a polymeric delivery system. We demonstrate that synthetic biodegradable polymers, poly-D,L-lactic acid-polyethylene glycol (PLA-PEG) block copolymers, which exhibit an exquisite temperature-dependent liquid-semisolid transition, work well as an injectable delivery system for recombinant human (rh) BMP-2. The thermosensitive property of the PLA-PEG/rhBMP-2 composite is permissive to percutaneous injection when heated. The fluidity of this composite decreases as it cools down to body temperature and the resultant semisolid form provides a scaffold for bone formation through the gradual local release of the rhBMP-2. This new type of injectable osteoinductive material will enable a less invasive approach to surgeries involving the restoration or repair of bone tissues.

Animals↗

PubMed2001

Amino acid sequences flanking polyglutamine stretches influence their potential for aggregate formation.

Expanded polyglutamine stretches have been shown to form aggregates and to be toxic to cells. In this study, we hypothesized that amino acid sequences flanking the polyglutamine stretches influence the aggregate formation potential of these stretches. Green fluorescent protein (GFP) fusion proteins containing glutamine repeats of various lengths and a fixed number of flanking amino acids of ataxin-2, huntingtin, dentatorubral-pallidoluysian atrophy protein (DRPLAP) or ataxin-3 were transiently expressed in COS-7 cells. The aggregate formation potential of ataxin-2 and DRPLAP increased in a CAG-repeat-length-dependent manner, with a threshold between 34 and 36. Truncated ataxin-2-Q56-GFP and truncated huntingtin-Q56-GFP showed a significantly higher aggregate formation potential than truncated DRPLAP-Q56-GFP or truncated ataxin-3-Q56-GFP. These results are in agreement with the clinical observation that ages of disease onset in patients with spinocerebellar ataxia type 2 or Huntington's disease are lower than those in patients with DRPLA or Machado-Joseph disease having expanded CAG repeats of the same length. Furthermore, mutagenesis of the flanking sequence of ataxin-2 markedly reduced its aggregate formation potential. These results indicate that the amino acid sequences flanking the polyglutamine stretches significantly influence their aggregate formation potential.

Amino Acid Sequence↗

PubMed2001

Two starch-branching-enzyme isoforms occur in different fractions of developing seeds of kidney bean.

The nature and enzymic properties of starch-branching enzyme (SBE) are two of the dominant factors influencing the fine structure of starch. To understand the role of this enzyme's activity in the formation of starch in kidney bean (Phaseolus vulgaris L.), a study was undertaken to identify the major SBE sequences expressed during seed development and to characterize the enzymic properties of the coded recombinant enzymes. Two SBE cDNA species (designated pvsbe2 and pvsbe1) that displayed significant similarity (more than 70%) to other family A and B SBEs respectively were isolated. Northern blot analysis revealed that pvsbe1 and pvsbe2 were differentially expressed during seed development. pvsbe2 showed maximum steady-state transcript levels at the mid-stage of seed maturation, whereas pvsbe1 reached peak levels at a later stage. Western blot analysis with antisera raised against both recombinant proteins (rPvSBE1 and rPvSBE2) showed that these two SBEs were located in different amyloplast fractions of developing seeds of kidney bean. PvSBE2 was present in the soluble fraction, whereas PvSBE1 was associated with the starch granule fraction. The differences in location suggest that these two SBE isoenzymes have different roles in amylopectin synthesis in kidney bean seeds. rPvSBE1 and rPvSBE2 were purified from Escherichia coli and their kinetic properties were determined. The affinity of rPvSBE2 for amylose (K(m) 1.27 mg/ml) was lower than that of rPvSBE1 (0.46 mg/ml). The activity of rPvSBE2 was stimulated more than 3-fold in the presence of 0.3 M citrate, whereas rPvSBE1 activity was not affected. The implications of the enzymic properties and the distribution of SBEs and amylopectin structure are discussed.

1,4-alpha-Glucan Branching Enzyme↗

PubMed2001

A new recombinant human bone morphogenetic protein-2 carrier for bone regeneration.

A gelatin sponge was formed by foaming and heat treating a gelatin solution, followed by coating the solid with poly(D,L-lactic-co-glycolic acid) to reinforce the gelatin framework. This sponge was tested for its suitability as a biodegradable porous, recombinant human bone morphogenetic protein (rhBMP)-2 carrier. Incorporation of rhBMP-2 into the sponge was closely related to its bulk density of gelatin sponge. The calcium content in the sponges, as assessed by an ectopic bone formation assay in rats, increased with the increasing sponge bulk density. Histologic and peripheral quantitative computed tomography analysis of implants in this ectopic assay system revealed cell growth throughout the carrier in 4 weeks after implantation regardless gelatin bulk density. The carrier containing rhBMP-2 maintained its three-dimensional structure after implantation; the carrier resisted collapse caused by soft tissue pressure during rapid bone formation as assessed by soft X-ray photographs. These results indicate that this newly developed sponge has excellent carrier characteristics to introduce rhBMP-2 into areas needed for bone regeneration.

Animals↗

PubMed2001

Renormalization-group theoretical reduction.

It has been known for some time that singular perturbation and reductive perturbation can be unified from the renormalization-group (RG) theoretical point of view. However, renormalization-group approaches to singularly perturbed problems require explicit perturbation results, so they could be complicated practically. The approach proposed in this paper has considerably eliminated the need for explicit perturbation results, making the RG approach simpler than many conventional singular perturbation approaches. Consequently, we may assert that reductive extraction of global features of the problem is the essence of singular perturbation methods.

Journal Article↗

PubMed2001

Predominant 1,2-insertion of styrene in the Pd-catalyzed alternating copolymerization with carbon monoxide.

The regioselectivity of styrene insertion to an acyl-Pd bond was studied by NMR in (i) a stoichiomeric reaction and (ii) a copolymerization with CO. In the stoichiometric reaction of styrene with [(CH(3)CO)Pd(CH(3)CN)[(R,S)-BINAPHOS]].[B[3,5-(CF(3))(2)C(6)H(3)](4)], both 1,2- and 2,1-products were given. To mimic the real polymerization conditions, a polyketone-substituted complex [[CH(3)(CH(2)CHCH(3)CO)(n)]Pd[(R,S)-BINAPHOS]].[B(3,5-(CF(3))(2)C(6)H(3))(4)] (n approximately 14) was prepared. When this polymer-attached Pd species was treated with styrene, the 1,2-insertion product was the only detectable species. Thus, exclusive 1,2-insertion is demonstrated to be responsible for the styrene-CO copolymerization, in sharp contrast to the predominant 2,1-insertion with conventional nitrogen ligands. Chain-end analysis revealed that beta-hydride elimination took place from the 2,1-complex but not from the 1,2-complex. Thus, once 2,1-insertion occurs, rapid beta-hydride elimination proceeds to terminate the polymerization, as is common to the other phosphorus-ligand systems. The resulting Pd-H species re-initiates the copolymerization, as was proven by MALDI-TOF mass analysis of the product copolymers.

Journal Article↗

PubMed2001

Cesarean section in a patient with syringomyelia.

PURPOSE: To describe the anesthetic management of Cesarean section in a patient with syringomyelia. CLINICAL FEATURES: A 27-yr-old pregnant woman with syringomyelia was scheduled to undergo elective Cesarean section. At the age of 25 yr, she had begun to experience headaches, and at the age of 26 yr, a diagnosis of syringomyelia of the upper spinal cord was made on the basis of magnetic resonance imaging findings. No symptoms other than headache were noted preoperatively. General anesthesia was used for the Cesarean section. After the administration of 1 mg vecuronium as a priming dose, 5 mg vecuronium were injected. At the onset of clinical muscle weakness, 225 mg thiamylal were promptly administered as the induction agent and the patient was intubated (timing principle with priming method) and pressure on the cricoid cartilage applied to prevent regurgitation of stomach contents. Anesthesia was maintained with oxygen, nitrous oxide and isoflurane at a low concentration. Mild hyperventilation was used throughout the procedure. Anesthesia and surgery proceeded without any problem, response to vecuronium was clinically normal and recovery was uneventful. Neurological status remained normal. CONCLUSION: We report the safe use of general anesthesia for Cesarean section in a patient with syringomyelia. Precautions were taken to avoid increases in intracranial pressure and our patient experienced no untoward neurologic event.

Adult↗

PubMed2001

A biodegradable polymer as a cytokine delivery system for inducing bone formation.

Bone morphogenetic proteins (BMPs) that have the potential to elicit new bone in vivo have been used in a tissue-engineering approach for the repair of bone injuries and bone defects. Although it is now possible to generate large amounts of recombinant human (rh) BMPs for medical use, the major challenge remains in the development of optimal local delivery systems for these proteins. Here we describe the development of a synthetic biodegradable polymer, poly-d,l-lactic acid-p-dioxanone-polyethylene glycol block copolymer (PLA-DX-PEG). This polymer exhibits promising degradation characteristics for BMP delivery systems and good biocompatibility under test conditions. PLA-DX-PEG/rhBMP-2 composite implants induced ectopic new bone formation effectively when tested in vivo, and can repair large bone defects orthotopically. This polymeric delivery system represents an advance in the technology for the enhancement of bone repair.

Animals↗

PubMed2001

nhaG Na(+)/H(+) antiporter gene of Bacillus subtilis ATCC9372, which is missing in the complete genome sequence of strain 168, and properties of the antiporter.

We cloned a gene which enabled Escherichia coli mutant host cells lacking all of the major Na(+)/H(+) antiporters to grow in the presence of 0.2 M NaCl from chromosomal DNA of Bacillus subtilis ATCC9372. An Na(+)/H(+) antiport activity was observed with membrane vesicles prepared from E. coli cells possessing the cloned gene, but not with vesicles from the host cells. Lithium ion was also a substrate for the antiporter. We sequenced the cloned DNA and found one open reading frame (designated nhaG) preceded by a promoter-like sequence and a Shine-Dalgarno sequence, and followed by a terminator-like sequence. The deduced amino acid sequence of NhaG suggested that it consisted of 524 residues and that the calculated molecular mass was 58.1 kDa. None of the bacterial Na(+)/H(+) antiporters so far reported, except NhaP of Pseudomonas aeruginosa and SynNhaP (NhaS1) of Synechocystis sp., showed significant sequence similarity with the NhaG. However, the NhaP, the SynNhaP, animal NHEs (Na(+)/H(+) exchangers), and some hypothetical Na(+)/H(+) antiporters of several organisms showed significant sequence similarities with the NhaG. Interestingly, the entire DNA region corresponding to the nhaG gene is missing in the reported complete genome sequence of B. subtilis strain 168. We detected a band that hybridized with the nhaG DNA in chromosomal DNA from B. subtilis ATCC9372 but not with that from strain 168. The missing DNA region (1,774 base pairs) is sandwiched by two identical sequences, TTTTCTT.

Animals↗

PubMed2001

Clinicopathologic and immunohistochemical features and microsatellite status of endometrial cancer of the uterine isthmus.

To clarify the clinicopathologic, molecular, and immunohistochemical characteristics of uterine isthmic endometrial cancer (UIE), we examined 13 cases of UIE and compared them with 33 cases of endometrial cancer of the uterine corpus (UCE) with respect to clinicopathologic factors, the expression of p53, the estrogen receptor (ER) and the progesterone receptor (PR) status, DNA ploidy, and microsatellite instability (MSI). Five (38.4%) of the UIE patients had stage I, two (15.4%) had stage II, and six (46.2%) had stage III disease (FIGO 1988). Myometrial invasion was confirmed in 92.3% of the UIE patients, and these patients had a higher (p < 0.05) frequency of > 50% myometrial invasion (46.2%) than the patients with UCE (15.2%). Moreover, the UIE patients had a higher frequency of positive peritoneal cytology (p < 0.05) and pelvic lymph node metastases (p < 0.05). No UIE tumors exhibited MSI, and the tumors in these patients had a higher expression of p53 (p < 0.01), a lower expression of ER (p < 0.05) and PR (p < 0.05), and a higher frequency of DNA aneuploidy (p < 0.01) than the UCE tumors. These findings suggest that the UIE is clearly different from UCE in the clinicopathologic, immunohistochemical features, and microsatellite status.

Aneuploidy↗

PubMed2001

Major isoforms of starch branching enzymes in premature seeds of kidney bean (Phaseolus vulgaris L.).

Developing seeds of the kidney bean (Phaseolus vulgaris L.) contain several isoforms of starch branching enzymes. Two of them, KBE1 and KBE2, which are the major forms in the premature seeds, were purified as a single band of protein on SDS-PAGE and native PAGE by chromatographies on DEAE-Sepharose, Bio-Gel P-200, and amylose-binding Sepharose 6B. The enzymes had similar pH optimum (7.0), pH stability (7.0-9.5), temperature optimum (25-30 degrees C), and temperature stability (up to 40 degrees C). Additionally, both were inhibited by various divalent metal ions and activated by citrate. Finally, though their N-terminal amino acid sequences were identical, their molecular masses and affinities for amylose differed; 80 kDa and 1.27 mM for KBE1 and 77 kDa and 0.74 mM for KBE2.

1,4-alpha-Glucan Branching Enzyme↗

PubMed2001

Mitogen-activated protein kinases and cerebral ischemia.

Mitogen-activated protein kinases (MAPKs) have crucial roles in signal transduction from the cell surface to the nucleus and regulate cell death and survival. Recent papers support the hypothesis that neuronal apoptosis and cerebral ischemia induce the robust activation of MAPK cascades. Although extracellular signal-regulated kinases pathways promote cell survival and proliferation, and c-Jun N-terminal protein kinases/p38 pathways induce apoptosis in general, the roles of MAPK cascades in neuronal death and survival seem to be complicated and altered by the type of cells and the magnitude and timing of insults. Some specific inhibitors of MAPK cascades provide important information in clarifying the roles of each molecule in neuronal death and survival, but the results are still controversial. Further studies are necessary to elucidate the activated signal transduction upstream and downstream of the cascades in cerebral ischemia, and to define the crosstalk between the cascades and other signaling pathways, before MAPK cascades can be candidate molecules in the treatment of cerebral ischemia.

Animals↗